In 'mammals, the LH surge produce dramatic changes on the ovarian follicle that culminate with ovulation of a fertilizable egg. However, the biochemical mechanisms that allow propagation of the LH stimulus from the surface of the follicle are unknown. This proposal will test the hypothesis that LH signals oocyte maturation arid cumulus expansion via release of EGF-like growth factors. Preliminary data show that expression; of these growth factors is rapidly activated by LH and that these growth factors mimic some of the LH effects in vitro. To further understand the role of this EGF network in the follicle, experiments are organized along two specific aims. With aim 1, fertility, fecundity, and ovulation-related events in mice deficient in EGF-like growth factors or in compound mutant mice bearing defects in growth factors and related receptors will be analyzed. With Aim 2, the mechanism of processing of EGF-like growth factors in granulosa cells of the follicle will be investigated. These studies will provide evidence for the role of the EGF network in the ovarian follicle during ovulation. Understanding this paracrine regulation will provide new insight into ovarian physiology. It will also open new avenues for assisted reproduction and pharmacological intervention to manipulate fertility.